PROJECT SUMMARY/ABSTRACT The objectives of this K01 award are twofold: (1) to enable the candidate to obtain the additional training required for an independent research career investigating self-regulatory pathways of risk for adolescent externalizing problems and substance use, with a focus on early life environmental exposures; and (2) to leverage the infrastructure from an existing parent study of smoke exposure during pregnancy and the immediate postpartum period to conduct baseline, 6- and 12-month follow-ups of the sample (currently ages 10-13 years old) and advance knowledge of self-regulatory pathways linking early smoke exposure to offspring substance use, ADHD symptoms, and conduct problems. Due to the high prevalence and fiscal and societal consequences of early life smoke exposure, understanding the pathways linking smoke exposure to offspring externalizing problems and substance use may attenuate a major public health concern. Therefore, the aims of this project are to: examine the effects of early smoke exposure on adolescent self-regulation, substance use and externalizing (ADHD symptoms, conduct problems; aim 1); explore links between self-regulation at the K01 study baseline and substance use and externalizing at 6- and 12-month follow-ups (aim 2a); and identify self-regulation problems at the K01 study baseline that mediate early smoke exposure and level of, and change in substance use and externalizing severity over time (aim 2b). This project will extend the study of a unique sample to characterize the neurobehavioral effects of early smoke exposure as children transition to adolescence, a developmental period that is vital for the development of self-regulation, as well as increased risk for substance use and externalizing behavior. This research will identify self-regulation outcomes most influenced by early smoke exposure and their relations to externalizing problems and substance use. Self- regulation is malleable and self-regulation interventions improve substance use and externalizing behavior. Therefore, findings from this study may help to identify children at greatest risk for future externalizing and substance use problems and determine potential avenues for intervention, which may reduce the public health impact of these problems. This K01 award will also allow the candidate the time and training required to build on her existing strengths and facilitate her transition to an independent scientist. To pursue this long-term research agenda, the Brown University Center for Alcohol and Addiction Studies-based candidate will work with experienced mentors to achieve the following training goals: (1) Obtain expertise in measuring and evaluating the effects of early smoke exposure; (2) Develop expertise in research design and methodology to comprehensively assess adolescent self-regulation; (3) Develop expertise in the assessment of adolescent substance use and externalizing (ADHD symptoms, conduct problems); and (4) Learn to apply advanced statistical methods for analyzing developmental data. This K01 addresses a NIDA priority to characterize developmental factors that mediate risk and resilience for drug use and addiction.